THE EFFECTS OF THE TIMING OF ETHANOL EXPOSURE DURING THE BRAIN GROWTH SPURT ON THE NUMBER OF CEREBELLAR PURKINJE AND GRANULE CELL NUCLEAR PROFILES

THE EFFECTS OF THE TIMING OF ETHANOL EXPOSURE DURING THE BRAIN GROWTH SPURT ON THE NUMBER OF CEREBELLAR PURKINJE AND GRANULE CELL NUCLEAR PROFILES
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DOI:
10.1111/j.1530-0277.1993.tb00808.x
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发表时间:
1993-06-01
影响因子:
3.2
通讯作者:
WEST, JR
WEST, JR
中科院分区:
医学3区
文献类型:
--
作者:
HAMRE, KM;WEST, JR

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发育过程中的乙醇暴露对小脑浦肯野细胞和颗粒细胞特别有害,但这种敏感性的机制和影响它的变量仍然未知。一个尚未充分研究的重要变量是乙醇暴露的时间。在大脑生长突增期暴露于乙醇会导致小脑蚓部10个小叶中浦肯野细胞的差异性丢失。然而,在大脑生长突增期改变乙醇暴露的时间是否会改变小脑蚓部浦肯野细胞丢失的程度和位置还没有研究。此外,小脑颗粒细胞的损失已被证明与浦肯野细胞的损失平行,从而得出结论,颗粒细胞的损失是其靶细胞浦肯野细胞损失的函数。本研究的目的是解决这两个问题。在以下2天时间段之一,通过人工饲养方法将雄性大鼠幼仔暴露于乙醇:出生后(PD)4-5、5-6、6-7、7-8、8-9、9-10或12-13天。还包括胃造口对照组(GC)和胃造口对照组(SC)。在PD 21处死所有幼仔。在所有组中对三个蚓部切片的浦肯野细胞核轮廓数量进行计数,而在选定组中估计10个小叶中颗粒细胞核轮廓数量。在PD 7 -8或任何后续暴露时间暴露于乙醇的幼仔中未观察到浦肯野细胞损失。此外,在观察到显著浦肯野细胞丢失的三个暴露组(PD 4 -5、PD 5 -6和PD 6 -7)中,7个小叶表现出显著差异,尤其是在PD 4 -5和PD 6 -7组之间。浦肯野细胞(PD 4 -5)损失最大的组也是颗粒细胞损失最大的组。颗粒细胞的显著损失没有发生,而相应的浦肯野细胞的损失。浦肯野细胞和颗粒细胞的损失受到乙醇暴露时间的影响,并且浦肯野细胞损失的程度和位置对乙醇暴露时间的影响非常敏感。
Ethanol exposure during development is particularly deleterious to cerebellar Purkinje cells and granule cells, but the mechanism(s) underlying this sensitivity and the variables which affect it remain unknown. One important variable that has not been fully investigated, is the timing of the ethanol exposure. Ethanol exposure during the brain growth spurt causes a differential loss of Purkinje cells across the 10 lobules of the vermal cerebellum. However, whether or not changing the timing of the ethanol exposure during the brain growth spurt alters the extent and location of the loss of Purkinje cells within the cerebellar vermis has not been investigated. Moreover, the loss of cerebellar granule cells has been shown to parallel the loss of Purkinje cells, leading to the conclusion that the loss of granule cells occurred as a function of the loss of their targets, the Purkinje cells. The purpose of this study was to address both issues. Male rat pups were exposed to ethanol, via an artificial-rearing method, during one of the following 2-day time periods: postnatal days (PD) 4-5, 5-6, 6-7, 7-8, 8-9, 9-10, or 12-13. Gastrostomy control (GC) and suckle control (SC) groups also were included. All pups were sacrificed on PD21. The number of Purkinje cell nuclear profiles from three vermal sections were counted in all groups, while the number of granule cell nuclear profiles in the ten lobules was estimated from pups in selected groups. No loss of Purkinje cells was observed in pups exposed to ethanol on PD7-8 or at any of the later exposure times. Additionally, among the three exposure groups in which significant Purkinje cell loss was observed (PD4-5, PD5-6 and PD6-7), seven lobules exhibited significant differences particularly between the PD4-5 and PD6-7 groups. The group with the greatest loss of Purkinje cells (PD4-5) also was the group with the greatest loss of granule cells. A significant loss of granule cells did not occur without a corresponding loss of Purkinje cells. The loss of both the Purkinje and granule cells was affected by the timing of the ethanol exposure, and that the extent and the location of Purkinje cell loss were extremely sensitive to the effects of the timing of the ethanol exposure.